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1.
Respir Med ; 204: 106990, 2022.
Article in English | MEDLINE | ID: mdl-36283245

ABSTRACT

INTRODUCTION: Bronchoscopic sampling of pulmonary lesions suspicious for lung cancer is frequently nondiagnostic. A genomic sequencing classifier utilizing bronchial brushings obtained at the time of the bronchoscopy has been shown to provide an accurate reclassification of the risk of malignancy (ROM) based on pre-procedure risk. Our objectives for this study were to determine the frequency with which the classifier up- or down-classifies risk in regular clinical practice and to model the potential clinical utility of that reclassification. METHODS: This observational study retrospectively assessed data from four clinical sites that regularly use the genomic classifier in the bronchoscopic evaluation of indeterminate lesions. Demographics and pre-bronchoscopy ROM were recorded. The frequency of up- and down-classification was calculated. Modeling based on reclassification rates and the performance characteristics of the classifier was performed to demonstrate the potential clinical utility of the result. RESULTS: 86 patients who underwent classifier testing following a nondiagnostic bronchoscopy were included. 45% of patients with high ROM prior to bronchoscopy were reclassified very high-risk. 38% of patients with intermediate ROM were up-or down-classified. 56% of patients with low ROM were reclassified to very low-risk. Overall, 42% of patients had a change in classification. 35% of the study cohort could potentially have avoided additional unnecessary procedures with subsequent guideline-adherent management. CONCLUSIONS: The classifier can guide decision-making following a nondiagnostic bronchoscopy, reclassifying risk in a significant percentage of cases. Use of the classifier should allow more patients with early-stage cancer to proceed directly to curative therapy while helping more patients with benign disease avoid further unnecessary procedures.


Subject(s)
Bronchoscopy , Lung Neoplasms , Humans , Bronchoscopy/methods , Retrospective Studies , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Genomics/methods , Lung/pathology
2.
Int J Mol Sci ; 23(2)2022 Jan 06.
Article in English | MEDLINE | ID: mdl-35054780

ABSTRACT

Double-strand breaks (DSB) are one of the most lethal forms of DNA damage that, if left unrepaired, can lead to genomic instability, cellular transformation, and cell death. In this work, we examined how repair of transcription activator-like effector nuclease (TALEN)-induced DNA damage was altered when knocking out, or inhibiting a function of, two DNA repair proteins, XRCC4 and MRE11, respectively. We developed a fluorescent reporter assay that uses TALENs to introduce DSB and detected repair by the presence of GFP fluorescence. We observed repair of TALEN-induced breaks in the XRCC4 knockout cells treated with mirin (a pharmacological inhibitor of MRE11 exonuclease activity), albeit with ~40% reduced efficiency compared to normal cells. Editing in the absence of XRCC4 or MRE11 exonuclease was robust, with little difference between the indel profiles amongst any of the groups. Reviewing the transcriptional profiles of the mirin-treated XRCC4 knockout cells showed 307 uniquely differentially expressed genes, a number far greater than for either of the other cell lines (the HeLa XRCC4 knockout sample had 83 genes, and the mirin-treated HeLa cells had 30 genes uniquely differentially expressed). Pathways unique to the XRCC4 knockout+mirin group included differential expression of p53 downstream pathways, and metabolic pathways indicating cell adaptation for energy regulation and stress response. In conclusion, our study showed that TALEN-induced DSBs are repaired, even when a key DSB repair protein or protein function is not operational, without a change in indel profiles. However, transcriptional profiles indicate the induction of unique cellular responses dependent upon the DNA repair protein(s) hampered.


Subject(s)
DNA Breaks, Double-Stranded , DNA Repair , DNA-Binding Proteins/genetics , MRE11 Homologue Protein/genetics , RNA-Seq , Transcription Activator-Like Effector Nucleases/toxicity , DNA/metabolism , Gene Knockout Techniques , HeLa Cells , Humans , MRE11 Homologue Protein/antagonists & inhibitors , Transcription Activator-Like Effector Nucleases/metabolism
3.
Microbiol Resour Announc ; 10(1)2021 Jan 07.
Article in English | MEDLINE | ID: mdl-33414284

ABSTRACT

We report the 3.7-Mb genome sequence of strain SS-5, a magnetotactic, sulfur-oxidizing rod and member of the family Chromatiaceae of the class Gammaproteobacteria, which biomineralizes membrane-bound, elongated, prismatic octahedral, magnetite nanocrystals. This genome sequence brings further diversity for understanding the origin and evolution of magnetotaxis and magnetosome biomineralization.

4.
Microbiol Resour Announc ; 9(1)2020 Jan 02.
Article in English | MEDLINE | ID: mdl-31896630

ABSTRACT

We report the complete 4.1-Mb genome sequence of strain BW-2, a magnetotactic, sulfur-oxidizing rod, belonging to the family Ectothiorhodospiraceae of the class Gammaproteobacteria, that biomineralizes membrane-bounded magnetite nanocrystals in its magnetosomes. This genome sequence, in comparison with those of other magnetotactic bacteria, is essential for understanding the origin and evolution of magnetotaxis and magnetosome biomineralization.

5.
Environ Microbiol ; 18(12): 4426-4441, 2016 12.
Article in English | MEDLINE | ID: mdl-27241114

ABSTRACT

Magnetotactic bacteria (MTB) are a heterogeneous group of ubiquitous aquatic microorganisms capable of biomineralizing nano-sized, membrane-bound, magnetic iron-rich mineral particles called magnetosomes. MTB are found in chemically-stratified aquatic sediments and/or water columns with a wide range of salinities, moderate to high temperatures, and pH varying from neutral to strongly alkaline. MTB from very cold environments have not been investigated to any great degree and here we characterize MTB from the low temperature Antarctic maritime region. Sediment samples were collected at nine sampling sites within Admiralty Bay, King George Island (62°23'S 58°27'W) from 2009 to 2013. Samples from five sites contained MTB and those from two of these sites contained large number of magnetotactic cocci that were studied using electron microscopy and molecular techniques. The magnetotactic cocci contained magnetosomes either arranged as two or four chains or as a disorganized cluster. The crystalline habit and composition of all magnetosomes analyzed with high-resolution transmission electron microscopy and energy dispersive X-ray microanalysis were consistent with elongated prismatic crystals of magnetite (Fe3 O4 ). The retrieved 16S rRNA gene sequences from magnetically-enriched magnetotactic cocci clustered into three distinct groups affiliated with the Alphaproteobacteria class of the Proteobacteria. Novel sequences of each phylogenetic cluster were confirmed using fluorescent in situ hybridization. Metagenomic data analysis of magnetically-enriched magnetotactic cocci revealed the presence of mam genes and MTB-specific hypothetical protein coding genes. Sequence homology and phylogenetic analysis indicated that predicted proteins are related to those of cultivated alphaproteobacterial MTB. The consistent and continuous low temperature of the sediment where the magnetotactic cocci are present (always below 1°C) suggests that these MTB from maritime Antarctica are psychrophiles. Moreover, similar morphotypes and 16S gene sequences were retrieved from samples collected from different sites from maritime Antarctica for several years suggesting that these new strains of MTB are indigenous members of Antarctic microbiota.


Subject(s)
Alphaproteobacteria/isolation & purification , Geologic Sediments/microbiology , Seawater/microbiology , Alphaproteobacteria/classification , Alphaproteobacteria/genetics , Alphaproteobacteria/growth & development , Antarctic Regions , Culture Media/chemistry , Culture Media/metabolism , DNA, Bacterial/genetics , Geologic Sediments/chemistry , In Situ Hybridization, Fluorescence , Magnetosomes , Microscopy, Electron, Transmission , Phylogeny , RNA, Ribosomal, 16S/genetics , Salinity , Seawater/chemistry
6.
Genome Announc ; 2(4)2014 Jul 31.
Article in English | MEDLINE | ID: mdl-25081260

ABSTRACT

Desulfonatronum thiodismutans strain MLF1, an alkaliphilic bacterium capable of sulfate reduction, was isolated from Mono Lake, California. Here we report the 3.92-Mb draft genome sequence comprising 34 contigs and some results of its automated annotation. These data will improve our knowledge of mechanisms by which bacteria withstand extreme environments.

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